Name of virus that causes influenza

Cedars-Sinai said it had recently seen one mild case of the co-infection. With the flu and COVID circulating at the same time, people can reduce the risk of becoming severely ill with either virus by getting vaccinated against the flu and COVID, wearing a mask in crowded spaces and washing your hands.

We'll notify you here with news about. Turn on desktop notifications for breaking stories about interest? Comments 0. As a result, the case mortality rate in the United States averaged 2. Moreover, mortality during the pandemic was concentrated in an unusually young age group 6. The age group affected most severely by the pandemic was that between 20 and 40 years, and this group accounted for almost half of influenza deaths during the pandemic.

The reasons for these unexpected patterns remain obscure. Influenza virus replicates in the epithelial cells throughout the respiratory tree, with virus being recoverable from both the upper and lower respiratory tract of people naturally or experimentally infected 2. As histologic changes are nonspecific, histologic analysis alone is insufficient to make a specific diagnosis 19 ; diagnosis typically requires supporting diagnostic tests such as viral isolation, rapid diagnostic tests including RT-PCR , serologic studies, or a biopsy or autopsy tissue section confirmed by in situ hybridization or immunohistochemical techniques Non-fatal influenza viral infections predominantly involve the upper respiratory tract and trachea, but fatal cases of influenza usually show evidence of pneumonia.

This review concentrates on the pathology of the lower respiratory tract. Starting with the first pathological studies of influenza associated with the pandemic 15 , 68 , 69 , involvement of epithelial cells lining the upper respiratory tract has been universally recognized and corresponds to the clinical signs and symptoms of pharyngitis and tracheobronchitis.

The large number of autopsy studies reported during and after the influenza pandemic all report such changes, particularly severe tracheitis. Winternitz and his coworkers, however, clearly recognized that the epithelium of the trachea, bronchi, and the pulmonary alveoli were primary sites of influenza viral replication.

They were among the only observers of the pandemic to reach such a conclusion At autopsy, the almost constant coexistence of secondary bacterial infections of the air passages in fatal interpandemic and pandemic influenza complicates the picture, making it difficult to ascribe observed changes solely to influenza virus infection.

In the acute stage, multifocal destruction and desquamation of the pseudostratified pseudostratified columnar epithelium of the trachea and bronchi are characteristic. Often only a basal layer of the epithelium remains. Edema and congestion of the submucosa are often marked These changes were carefully described by several distinguished pathologists in the aftermath of the influenza 20 , 70 — In later stages, Askanazy observed evidence of epithelial regeneration with the formation of a nonkeratinizing stratified squamous metaplasia in 38 of 90 cases Winternitz et al.

Lucke et al. The trachea and bronchi had markedly reddened and swollen mucosal surfaces, sometimes overlaid with mucopurulent material. The lumina contained large amounts of frothy blood-stained material. Their findings reiterate pathologic changes observed in and are concordant with the smaller number of influenza pathology studies published in recent decades.

Early structural changes caused by influenza virus in the epithelium of the upper airway are variable, including cytonecrosis initially involving shrinkage and vacuolization, followed by desquamation of these cells into the luminal space. Necrotic cells may also undergo phagocytosis by macrophages. These structural changes to the epithelium are often irregularly distributed, and regions of pathology can abut areas appearing histologically normal. The final stage of desquamation of the affected epithelium frequently shows only a single layer of flattened basalar epithelial cells covering the basement membrane.

Complete separation of the remaining epithelium may be a histologic artifact. An outstanding feature in early stages of infection is the absence of neutrophils in the infiltrate, but as epithelial cell necrosis occurs, these cells migrate in. Later stages show mononuclear inflammatory cell infiltrates in the walls of bronchi Opie 20 and Winternitz et al.

As in the overlying epithelium, changes consist of cytonecrosis and desquamation. Changes in the smaller airways are similar to those described above for larger airways. Goodpasture 75 described the pathology of small- and medium-sized bronchioles in Grossly, in early cases, the epithelial linings are erythematous and filled with thin blood-stained froth or fluid.

In later cases, the epithelia are necrotic. Because of the simpler structure of the bronchiolar epithelium, thinning and flattening of these cells can be more pronounced than in the larger airways.

Complete loss of the epithelial layer can be seen both ciliated and goblet cells , often associated with the formation of hyaline membranes at these sites. A neutrophilic exudate may be present in the bronchiolar lumen.

The interstitium may show congestion, edema, and an inflammatory infiltrate. Air spaces may be filled with edema, fibrin, and varying numbers of neutrophils They noted submucosal capillary congestion and thrombi and found that the bronchiolar wall was sometimes entirely necrotic and associated with a polymorphonuclear cell infiltrate.

Opie et al. Common changes include focal epithelial necrosis to necrosis of the entire wall, peribronchial hemorrhage, and peribronchial pneumonia. There is necrosis of the bronchiolar wall, with submucosal edema and vascular congestion. The epithelial layer is desquamating, and necrotic epithelial cells are present in the lumen.

There is necrosis of the bronchiolar wall. Influenza infection of the epithelium of the upper airway passages is also associated with vascular congestion and hyperemia, edema, and an inflammatory cell infiltration of the tunica propria and submucosa.

Infiltration of neutrophils penetrating from capillaries into virus-infected areas in the absence of any evidence of secondary bacterial infection may be observed; however, neutrophilic infiltration is never massive.

The presence of many neutrophils within the epithelial layer strongly suggests a coincident or secondary bacterial infection. A mononuclear-cell-inflammatory infiltrate of lymphocytes, histiocytes, and plasma cells is frequently found in the tunica propria and submucosa of influenza-infected airways.

Studies performed in the s and s 1 , and more recent studies 12 , 13 , have consistently demonstrated the presence of influenza virus in tracheobronchial epithelial cells. Like the variable and multifocal histopathology, staining is usually focal.

Both necrotic and histologically-normal-appearing cells can be positively stained. Mononuclear inflammatory cells may also stain positively. Mitotic activity in regenerating respiratory epithelium can be seen focally. In 11 cases in which death occurred in less than 5 days, they found variable mitotic activity but no evidence of true regeneration of the epithelial layer.

In pandemic material, they found 13 cases out of with regenerating epithelium 1. From these studies, and those of the pandemic 20 , it appears likely that in influenza infection epithelial regeneration starts after approximately 5 days. Chronic effects include squamous metaplasia and interstitial fibrosis Later stages show organizing diffuse alveolar damage, fibrosis, epithelial regeneration, and squamous metaplasia. Secondary or coincident bacterial pneumonias frequently occur and complicate the pathologic picture.

In such cases, a massive infiltration of neutrophils into alveolar air spaces is observed, and alveolar hemorrhage and edema are less pronounced than in primary influenza virus pneumonia An example of the massive neutrophil infiltration in acute bacterial bronchopneumonia is shown in Figure 3.

Additional changes associated with secondary bacterial pneumonias vary by causative agent and time course to death and are not further described in this review. Early pathologic descriptions of influenza pneumonia were made in the pandemic, depicting a gross pathologic picture of an edematous, hemorrhagic bronchopneumonia 15 , 68 , This fits the clinical picture of influenza viral pneumonia, as described by Leichtenstern in 15 , with patients showing marked dyspnea and developing cyanosis.

Influenza viral pneumonia patients often produce massive amounts of foamy, blood-tinged, or frankly hemorrhagic sputum Large-scale autopsy studies by prominent pathologists during the influenza pandemic first described the spectrum of changes associated with influenza virus pneumonia. Never before or since have so many pathological studies of influenza pneumonia been described. During the pandemic, an edematous, hemorrhagic bronchopneumonia often occurring concurrently with focal bacterial pneumonia was reported by many physicians and pathologists, compatible with findings reported in the aftermath of the pandemic.

Most notable among them are the classic pandemic studies by Goodpasture 75 , Klotz 76 , LeCount 14 , 77 , MacCallum 72 , Opie et al. Even though the first isolation of human influenza virus did not occur until 80 , many pathologists had long suspected an underlying primary influenza viral pneumonia could be described separately from secondary bacterial pneumonias.

Many pathologists in rejected the hypothesis that Bacillus now Haemophilus influenzae Pfeiffer's bacillus was the causative agent of influenza because in a number of series it was recovered in only a minority of cases at autopsy Wolbach performed large autopsy studies in Boston and at nearby Camp Devens during the pandemic 21 and in wrote,.

Pathologists who have reported on the pulmonary lesions have not always endeavored to separate the lesions due to the virus of the epidemic and those dependent on the complicating organisms. On account of the variety of complicating organisms, manifold gross pathologic appearances have been described, and a sharp separation between lesions produced by the virus of the epidemic disease and the complicating organisms has not been made One feels justified in formulating the opinion that influenza is a distinct disease, recognizable clinically only by its epidemiologic proportions and extreme infectiousness, characterized pathologically by peculiar lesions in the lungs, and caused by an unknown virus which gains entrance through the respiratory tract Wolbach described the hyaline membranes and the diffuse alveolar damage LeCount described the focal capillary and small vessel thromboses typical of influenza viral pneumonia MacCallum 72 and Winternitz et al.

The histopathologic pattern that emerged from these studies matches the modern view of viral pneumonia, with changes of diffuse alveolar damage, prominent necrosis of the alveolar epithelium, the formation of hyaline membranes in dilated alveolar ducts and alveoli, capillary thrombosis with necrosis of the alveolar septa necrotizing alveolitis , intraalveolar hemorrhage and edema, and cells with pyknotic nuclei in the alveolar air spaces desquamated alveolar epithelial cells.

During and after the pandemic, a number of excellent autopsy studies of influenza viral infection were reported 17 , 18 , 82 , One difference they noted was that acute alveolar edema was not as prominent a feature of influenza pneumonia as in , although it was still observed. In a reexamination of autopsy material of fatal interpandemic seasonal influenza cases from —, they reported that changes of primary influenza virus pneumonia were not frequently observed, although changes typical of influenza were seen in the air passages.

However, most interpandemic influenza cases had longer courses and secondary bacterial pneumonias. In the pandemic, other groups also reported on the pathologic changes observed in fatal influenza pneumonia cases 11 , 16 , Even though overall case mortality was low in the pandemic, as compared with the pandemic, the same spectrum of pathology was observed. In both the and pandemics, previously healthy individuals with no underlying chronic illnesses succumbed to fatal influenza viral pneumonias.

The alveolar epithelial cell lining is as much a target of influenza infection as the epithelial covering of the bronchi and bronchioles. Three characteristic alveolar changes are seen in early influenza virus pneumonia: capillary thrombosis, focal necrosis of the alveolar wall, and development of hyaline membranes.

Early lesions of the alveolar epithelium are often difficult to detect because of the hyperemic, partly hemorrhagic edematous pneumonia that develops with infection 1. Alveolar lining cells also undergo necrotic changes and desquamation.

Immunofluorescence studies documented influenza virus replication in alveolar epithelial cells in pandemic cases 1. Degenerative changes include cytoplasmic vacuolization and nuclear pyknosis. Vast numbers of desquamated cells may be observed in the luminal spaces of alveoli, alveolar ducts, and bronchioli together with macrophages showing phagocytosed cellular debris.

At a certain stage in influenza virus pneumonia, alveolar cells partially or completely disappear 20 , 72 , Late stages show the presence of regenerating alveolar epithelium type II alveolar hyperplasia 1 , These cytologic changes were observed in alveolar lining cells in influenza virus pneumonia, as described by MacCallum, in 11 of 44 cases. In 8 of these 11 cases, he also observed hyaline membranes, whereas 4 of 11 cases showed thromboses in the capillaries of the alveolar septa.

The cytologic changes are similar to those seen in ciliated cells of the upper air passages In affected areas, alveolar macrophages are sometimes present in large numbers and may show mitotic activity. They can demonstrate phagocytosis of degenerate, desquamated alveolar lining cells, leukocytes, and sometimes erythrocytes.

Some show degenerate changes and may also be infected primarily with influenza virus supported by in situ hybridization studies. Hyperemia of the alveolar wall caused by marked capillary congestion is invariably present in influenza virus pneumonia. The alveolar septa are considerably thickened by dilatation of the alveolar capillary bed. This dilatation is responsible for the diffuse red color of the affected areas Fibrinous capillary thrombi, first described by LeCount in , are found in both the walls of alveolar ducts and in the alveolar septa Leukocyte infiltration of the hyperemic alveolar septa is always present in the early stages of influenza virus pneumonia.

The leukocytes are predominantly neutrophils and occasionally eosinophils. Infiltration is never dense except in areas showing septal necrosis. When hyperemic alveolar septa show no leukocytic infiltration, the diagnosis of influenza pneumonia should be doubted.

Later stages of influenza virus pneumonia also show interstitial infiltrates of mononuclear leukocytes, predominantly lymphocytes and plasma cells. Megakaryocytes lying within the capillary bed are also commonly observed 1. Necrosis of the alveolar wall may be a result of capillary thrombosis The extent and number of necrotic sites vary. Necrotic areas are associated with leukocytic infiltrates, exudation of fibrin, and disappearance of alveolar lining cells.

Endothelial cell necrosis with pyknotic nuclei may be observed. Hemorrhage into the alveolar air spaces is often observed near necrotic areas, associated with the exudation of plasma and strands of fibrin. Alveolar air spaces adjacent to areas of necrosis of the alveolar walls usually contain an accumulation of desquamated alveolar cells 1 , A photomicrograph of necrotizing alveolitis with intraalveolar edema, fibrin, inflammatory cells, and desquamated alveolar epithelial cells is shown in Figure 4.

Hyaline membranes first appear in respiratory bronchioles and alveolar ducts, then develop on the alveolar walls 21 , as seen in a photomicrograph from another autopsy case Figure 5. In later stages usually after a clinical course of approximately one week , hyaline membranes may occur as coarse strands or fine strands merging into a network of fibrin in the alveolar air spaces. This picture of a meshwork of hyaline membranes within alveoli is a characteristic finding in fully developed influenza virus pneumonia.

Hyaline membranes may also be observed covering small epithelial defects in bronchioli and small bronchi. Intraalveolar edema and hemorrhage are outstanding features of influenza virus pneumonia. In general their presence is associated with necrosis of the alveolar wall. Dilatation of the alveolar ducts is also a common feature in the acute stage of fatal influenza virus pneumonia described by many authors in Intraalveolar hemorrhage is often, but not always, associated with areas of necrosis of the alveolar wall.

Hemorrhage can sometimes be extensive and may be grossly visible on a cut section as tiny or large hemorrhagic areas, and also beneath the pleura Figure 1 — This is a picture of a phylogenetic tree. Each sequence from a specific influenza virus has its own branch on the tree. The degree of genetic difference between viruses is represented by the length of the horizontal lines branches in the phylogenetic tree. The further apart viruses are on the horizontal axis of a phylogenetic tree, the more genetically different the viruses are to one another.

An influenza clade or group is a further subdivision of influenza viruses beyond subtypes or lineages based on the similarity of their HA gene sequences. See the Genome Sequencing and Genetic Characterization page for more information. Clades and subclades are shown on phylogenetic trees as groups of viruses that usually have similar genetic changes i. Dividing viruses into clades and subclades allows flu experts to track the proportion of viruses from different clades in circulation.

Note that clades and sub-clades that are genetically different from others are not necessarily antigenically different. These proteins act as antigens. Antigens are molecular structures on the surface of viruses that are recognized by the immune system and can trigger an immune response such as antibody production.

Therefore, for antigenically different viruses, immunity developed against one of the viruses will not necessarily protect against the other virus as well. Influenza A H3N2 viruses also change both genetically and antigenically.

Influenza A H3N2 viruses have formed many separate, genetically different clades in recent years that continue to co-circulate. Similar to influenza A viruses, influenza B viruses can then be further classified into specific clades and sub-clades. If you're fully vaccinated and are in an area with a high number of new COVID cases in the last week, the CDC also recommends wearing a mask indoors in public and outdoors in crowded areas or when you're in close contact with unvaccinated people.

Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press. This content does not have an English version. This content does not have an Arabic version. Overview Influenza is a viral infection that attacks your respiratory system — your nose, throat and lungs.

More Information Flu: When to see a doctor? Request an Appointment at Mayo Clinic. Mayo Clinic Minute: Why getting vaccinated for the flu is doubly important this season. More Information Flu shots Cold and flu viruses: How long can they live outside the body?

High-dose flu vaccines: How are they different from other flu vaccines? Share on: Facebook Twitter. Show references Jameson JL, et al.

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